Exposure to selected limonene oxidation products: 4-oxopentanal (4-OPA), 3-isopropenyl-6-oxo-heptanal (IPOH), 4-acetyl-1-methylcyclohexene (4-AMCH) induce oxidative stress and inflammation in human lung epithelial cell lines

Limonene oxidation products (LOPs) have gained interest owing to multiple reports on harmful health effects. Recently, it has been shown that the selected LOPs: 4-OPA, IPOH and 4-AMCH have sensory irritation effects in mice and increased inflammatory markers in human lung cells. The present study was therefore undertaken to investigate the potential capacity of 4-OPA, IPOH and 4-AMCH to cause cell membrane damage (by lactate dehydrogenase assay), oxidative stress (by fluorescence assay and liquid chromatography) and inflammation (by enzyme-linked immunosorbent assay) in human alveolar (A549) and bronchial (16HBE14o-) epithelial cell lines. The overall results suggest that 4-OPA, IPOH have cytotoxic effects on human pulmonary cells, and that this might be mediated by ROS: the highest concentration applied of IPOH [500 µM] enhanced ROS generation by 100-fold (A549) and a 230-fold change (16HBE14o-) compared to the baseline. 4-OPA [500 µM] increased ROS levels by 1.4-fold ± 0.3 (A549) and by 127-fold ± 10.5 (16HBE14o-), while treatment with 4-AMCH [500 µM] led to a 0.9-fold ± 0.2 (A549) and 49-fold ± 12.8 (16HBE14o-) increase. IPOH [500 µM] caused a decrease in the thiol-state balance (e.g. 2 h post-treatment, GSH : GSSG ratio was significantly reduced by 37% compared with the untreated 16HBE14o- cells). 4-OPA [500 µM] decreased the GSH:GSSG ratio by a 1.3-fold change in A549 cells and a 1.4-fold change in 16HBE14o- cells. No statistically significant decrease in the GSH:GSSG ratio in both A549 and 16HBE14o- cell lines was observed at 500 µM 4-AMCH. In addition, both IPOH and 4-OPA [31.2 µM] increased the amount of the inflammatory markers: RANTES, VEGF and EGF (e.g. 2.0-fold change of RANTES amount determined in 16HBE14o- cells treated with IPOH [31.2 µM]). On the other hand, neither cell lines treated with 4-AMCH [31.2 µM] released statistically significant amounts of the selected inflammatory markers.

LIPŞA Dorelia;  BARRERO Josefa;  COELHAN Mehmet; 

2017-12-06

PERGAMON-ELSEVIER SCIENCE LTD

JRC106911

0045-6535,   

http://www.sciencedirect.com/science/article/pii/S0045653517316466?via%3Dihub,    https://publications.jrc.ec.europa.eu/repository/handle/JRC106911,   

10.1016/j.chemosphere.2017.10.065,